{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T15:19:22Z","timestamp":1793200762488,"version":"4.5.0"},"posted":{"date-parts":[[2026,2,18]]},"group-title":"Molecular Biology","reference-count":77,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH","award":["R35GM118147"],"award-info":[{"award-number":["R35GM118147"]}]},{"name":"NIH","award":["U01DK127419"],"award-info":[{"award-number":["U01DK127419"]}]},{"name":"NSF","award":["EF2022182"],"award-info":[{"award-number":["EF2022182"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Long-range gene regulation underlies a variety of human developmental disorders including Cornelia de Lange syndrome\n                  <jats:sup>1<\/jats:sup>\n                  and polydactyly\n                  <jats:sup>2<\/jats:sup>\n                  . Cohesin-mediated loop extrusion and tether-like elements are two major mechanisms implicated in fostering long-range enhancer-promoter (E-P) contacts\n                  <jats:sup>3<\/jats:sup>\n                  . However, our understanding of the contributions of these mechanisms to the kinetics of E-P interactions is limited. Here we employ a combination of quantitative single-cell imaging, genetic manipulations and polymer simulations to examine the interplay of cohesin-mediated loop extrusion and tethering elements\n                  <jats:sup>4,5<\/jats:sup>\n                  in the timely activation of gene expression in living\n                  <jats:italic>Drosophila<\/jats:italic>\n                  embryos. Depletion of NIPBL or deletion of an enhancer-proximal CTCF anchor element reduced expression without changing the duration of individual transcriptional bursts. Genetic epistasis experiments recapitulated polymer simulations predicting complementation of tether deletions by augmenting the stability of cohesin via reduced levels of WAPL\n                  <jats:sup>6<\/jats:sup>\n                  . We propose a \u201cscan and snag\u201d model whereby directional cohesin-driven enhancer scanning promotes diffusion-mediated tethering interactions to produce successful E-P contacts and transcriptional activation. We discuss how modulating cohesin stability and the \u201cstickiness\u201d of looping factors\n                  <jats:sup>7\u201310<\/jats:sup>\n                  can fine-tune the levels and timing of gene expression in mammalian developmental and disease processes.\n                <\/jats:p>","DOI":"10.64898\/2026.02.17.706355","type":"posted-content","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T14:05:15Z","timestamp":1771423515000},"source":"Crossref","is-referenced-by-count":5,"title":["Loop Extrusion Accelerates Long-Range Enhancer-Promoter Searches in Living Embryos"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0387-913X","authenticated-orcid":false,"given":"Pavan","family":"Choppakatla","sequence":"first","affiliation":[{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleena L.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohn","family":"Borjigin","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Princeton University, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tee","family":"Udomlumleart","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Stanford University, Stanford, CA, USA"},{"name":"Department of Genetics, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Hu","sequence":"additional","affiliation":[{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9460-139X","authenticated-orcid":false,"given":"Thomas","family":"Gregor","sequence":"additional","affiliation":[{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, NJ, USA"},{"name":"Department of Developmental and Stem Cell Biology, CNRS UMR3738 Paris Cit\u00e9, Institut Pasteur, 75015 Paris, France"},{"name":"Joseph Henry Laboratories of Physics, Princeton University, Princeton, NJ 08544, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair N.","family":"Boettiger","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Levine","sequence":"additional","affiliation":[{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, NJ, USA"},{"name":"Department of Molecular Biology, Princeton University, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026022023000553000_2026.02.17.706355v1.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2201029119"},{"key":"2026022023000553000_2026.02.17.706355v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.04.004"},{"key":"2026022023000553000_2026.02.17.706355v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2024.102282"},{"key":"2026022023000553000_2026.02.17.706355v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04680-7"},{"key":"2026022023000553000_2026.02.17.706355v1.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi7178"},{"key":"2026022023000553000_2026.02.17.706355v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.04.013"},{"key":"2026022023000553000_2026.02.17.706355v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-020-0394-8"},{"key":"2026022023000553000_2026.02.17.706355v1.8","doi-asserted-by":"crossref","unstructured":"Habari, B. 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